When metabolic comorbidities and risk of malnutrition coexist: The new era of inflammatory bowel disease.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and risk of malnutrition can coexist in patients with inflammatory bowel disease (IBD). We performed a malnutrition risk assessment as part of the standard follow-up of IBD patients and studied the potential risk factors for being at risk of malnutrition based on the presence or absence of MASLD. METHODS: The Malnutrition Universal Screening Tool (MUST) was used to screen malnutrition risk (MUST ≥ 1) and controlled attenuation parameter (CAP ≥ 248 dB/min) to assess MASLD. Adherence to a Mediterranean diet, physical activity, and quality of life were also assessed. RESULTS: Of 686 evaluated IBD patients, 130 (18.9%) were identified as being at risk of malnutrition. Patients without MASLD (n=89 [68.5%]) were more likely to be at risk than those with MASLD (n=41 [31.5%], p=0.005). However, among patients at risk of malnutrition, those with MASLD were more likely to have active IBD (82.9%) than patients without MASLD (39.3%, p<0.001). Female sex (OR 1.984, p=0.027) and young age (OR 1.014, p=0.006) were associated with malnutrition risk only in patients with IBD without MASLD. Being at risk of malnutrition was associated with worse quality of life (p<0.001), especially in IBD patients with MASLD. CONCLUSIONS: Malnutrition risk and quality of life are modified by the presence of MASLD in IBD patients.

One-step non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis and fibrosis in high-risk population.

BACKGROUND AND AIM: Type 2 Diabetes mellitus (T2DM), age, and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess the performance of non-invasive tests (NITs) for the diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis in high-risk subjects. METHODS: Multicentre cross-sectional study that included 124 biopsy-proven MASLD in more than 50 years-old patients with overweight/obesity and T2DM. Vibration-controlled transient elastography, Fibrosis-4 index (FIB-4), Non-alcoholic fatty liver disease fibrosis score (NFS), OWLiver Panel (OWLiver DM2 + Metabolomics-Advanced Steatohepatitis Fibrosis Score -MASEF) and FibroScan-AST were performed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC) were calculated. NITs were assessed individually and in sequential/parallel combinations. RESULTS: 35 (28.2%) patients had early MASH and 66 (53.2%) had MASH with significant fibrosis (at-risk MASH). The OWLiver Panel correctly classified 86.1% as MASH, showing an accuracy, sensitivity, specificity, PPV, and NPV of 0.77, 0.86, 0.35, 0.85, and 0.36, respectively. Class III obesity, diabetes control, or gender did not impact on the performance of the OWLiver Panel (p > 0.1). NITs for at-risk MASH showed an AUC > 0.70 except for NFS. MASEF showed the highest accuracy and NPV for at-risk MASH (AUC 0.77 [0.68-0.85], NPV 72%) and advanced fibrosis (AUC 0.80 [0.71-0.88], NPV 92%). Combinations of NITs for the identification of at-risk MASH did not provide any additional benefit over using MASEF alone. CONCLUSION: One-step screening strategy with the OWLiver Panel has high accuracy to detect MASH and at-risk MASH in high-risk subjects for MASLD.

Metabolic dysfunction-associated steatotic liver disease and diabetes: the cross-talk between hepatologist and diabetologist.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (DM) are the most prevalent metabolic disorders globally. The numbers affected in both disorders are also rapidly increasing with alarming trends in children and young adults. AREAS COVERED: Insulin resistance (IR) and the subsequent metabolic dysregulation are the fundamental pathogenesis pathways of the prevalent metabolic disorders. The interaction and impacts are bidirectional between MASLD and DM in terms of disease mechanisms, disease course, risks, and prognosis. There's a pressing issue for highlighting the links between MASLD and DM for both care specialists as well as primary care providers. The review collected the scientific evidence addressing the mutual interactions between the two disorders. The strategies for surveillance, risk stratification, and management are discussed in a practical manner. It also provides individualized viewpoints of patient care in hepatology and diabetology. EXPERT OPINION: Both MASLD and DM shared similar disease mechanisms, and affected the disease development and progression in a bidirectional manner. The high prevalence and the cross-link between the two disorders raise clinical issues from awareness, screening, risk stratification, optimal referral, to appropriate management for primary care providers.

Incorporating artificial intelligence in portable infrared thermal imaging for the diagnosis and staging of nonalcoholic fatty liver disease.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is one of the most prevalent chronic liver diseases worldwide. Thermal imaging combined with advanced image-processing and machine learning analysis accurately classified disease status in a study on mice; this study aimed to develop this tool for humans. This prospective study included 46 patients who underwent liver biopsy. Liver thermal imaging was performed on the same day as liver biopsy. We developed an image-processing algorithm that measured the relative spatial thermal variation across the skin covering the liver. The texture parameters obtained from the thermal images were input into the machine learning algorithm. Patients were diagnosed with MASLD and stratified according to nonalcoholic fatty liver disease activity score (NAS) and fibrosis stage using the METAVIR score. Twenty-one of 46 patients were diagnosed with MASLD. Using thermal imaging followed by processing, detection accuracy for patients with NAS >4 was 0.72.

Outcome prediction in metabolic dysfunction-associated steatotic liver disease using stain-free digital pathological assessment.

Computational quantification reduces observer-related variability in histological assessment of metabolic dysfunction-associated steatotic liver disease (MASLD). We undertook stain-free imaging using the SteatoSITE resource to generate tools directly predictive of clinical outcomes. Unstained liver biopsy sections (n = 452) were imaged using second-harmonic generation/two-photon excitation fluorescence (TPEF) microscopy, and all-cause mortality and hepatic decompensation indices constructed. The mortality index had greater predictive power for all-cause mortality (index >.14 vs. .31 vs.

Assessment of HBV variants and novel viral and immune biomarkers in chronic hepatitis B patients with metabolic dysfunction associated steatotic liver disease.

Co-existing chronic hepatitis B virus (CHB) infection and metabolic dysfunction associated steatotic liver disease (MASLD) can exert complex effects on hepatic metabolism, requiring mechanistic study. CHB participants were assessed for MASLD and the impact of hepatic steatosis/metabolic syndrome (MetS) on novel viral and immunological markers. In this prospective, cohort study, untreated CHB subjects were assessed for liver disease by non-invasive tests (i.e. FibroScan, controlled attenuation parameter, CAP). Subjects were tested for cytokines and IFN-γ ELISPOT assay to HBV Surface (S) and Core (C) proteins. Standard HBV serological, exploratory biomarkers and deep sequencing of HBV S and C genes were performed. In 53 subjects (median age 45 years [SD = 10.6], 35% F, 56% Asian, 20% Black, 3% White), 94% (50) HBeAg negative, 63% genotype B/C, mean HBV DNA 3.2 log10 IU/mL (SD = 1.8), quantitative HBsAg 2.9 log10 IU/mL (SD = 1.2) and HBV pgRNA 2.1 log10 copies/mL (SD = 1.3). In enrolled subjects, the mean ALT was 41.9 U/L (SD = 24.0), FibroScan was 5.7 kPa (SD = 1.9) and CAP was 306.4 dB/m (SD = 49.0). The mean BMI was 28.2 kg/m2 (SD = 4.2), 20% (11/53) had diabetes, 35% (19/53) dyslipidaemia and 24% (13/53) hypertension. Subjects with MetS and steatosis showed lower HBV markers (p < .01), higher HBV S diversity (p = .02) and greater frequency of HBV variants associated with host-anti-viral immune escape. Pro-inflammatory cytokine levels and HBV-specific cellular responses were higher in participants with hepatic steatosis. In CHB, MASLD/hepatic steatosis was associated with HBV variants and systemic immune responses potentially impacting liver disease progression despite low-level viraemia.

MAFLD-related hepatocellular carcinoma: Exploring the potent combination of immunotherapy and molecular targeted therapy.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity globally, and with the prevalence of metabolic-related diseases, the incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) related hepatocellular carcinoma (MAFLD-HCC) continues to rise with the limited efficacy of conventional treatments, which has created a major challenge for HCC surveillance. Immune checkpoint inhibitors (ICIs) and molecularly targeted drugs offer new hope for advanced MAFLD-HCC, but the evidence for the use of both types of therapy in this type of tumour is still insufficient. Theoretically, the combination of immunotherapy, which awakens the body's anti-tumour immunity, and targeted therapies, which directly block key molecular events driving malignant progression in HCC, is expected to produce synergistic effects. In this review, we will discuss the progress of immunotherapy and molecular targeted therapy in MAFLD-HCC and look forward to the opportunities and challenges of the combination therapy.

Exploring non-invasive diagnostics for metabolic dysfunction-associated fatty liver disease.

The population with metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common worldwide. Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care. Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD, but it has associated risks and limitations. This has spurred the exploration of non-invasive diagnostics for MAFLD, especially for steatohepatitis and fibrosis. These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements, serum tests, imaging or stool metagenome profiling. However, they still need rigorous and widespread clinical validation for the diagnostic performance.

Association between composite dietary antioxidant index and metabolic dysfunction associated steatotic liver disease: result from NHANES, 2017-2020.

Background: The development of metabolic dysfunction associated steatotic liver disease (MASLD) has been associated with lipid accumulation, oxidative stress, endoplasmic reticulum stress, and lipotoxicity. The Composite Dietary Antioxidant Index (CDAI) is a comprehensive score representing an individual intake of various dietary antioxidants, including vitamin A, vitamin C, vitamin E, selenium, zinc, and carotenoids. This study investigated the association between CDAI and MASLD. Materials and methods: Clinical and demographic data, as well as ultrasound transient elastography measurements at baseline, were collected from the National Health and Nutrition Examination Survey 2017-2020 (NHANES 2017-2020). The controlled attenuation parameter was utilized to diagnose the presence of hepatic steatosis and to categorize individuals into those with and without MASLD. Liver stiffness was measured by ultrasound transient elastography, and subjects were classified as those with and without advanced liver fibrosis. Results: This study included 5,884 adults, of whom 3,433 were diagnosed with MASLD, resulting in a weighted prevalence of 57.3%. After adjusting for covariates, the odds ratios for MASLD were 0.96 (95% CI: 0.82, 1.12) in the second quartile, 0.80 (95% CI: 0.68, 0.95) in the third quartile and 0.60 (95% CI: 0.49, 0.73) in the fourth quartile, respectively. CDAI, however, was not significantly associated with advanced liver fibrosis. Conclusion: These findings suggested that scores on the CDAI were linearly and negatively associated with the prevalence of MASLD in the United States adults.

Silymarin decreases liver stiffness associated with gut microbiota in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. OBJECTIVE: To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. METHOD: In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. RESULTS: Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. CONCLUSION: These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

Hypolipidemia due to Familial Hypobetalipoproteinemia in Adolescents.

Background/Objective: Individuals with heterozygous familial hypobetalipoproteinemia (h-FHBL) due to loss-of-function mutation in the apolipoprotein B gene are typically asymptomatic with mild liver dysfunction, which is often detected incidentally. About 5% to 10% of those with h-FHBL develop steatohepatitis which occasionally progress to cirrhosis especially in the presence of alcohol use, excess calorie consumption, or liver injury. We report 3 patients with hypobetalipoproteinemia, 2 with confirmed h-FHBL, and 1 with suspected h-FHBL. Case Report: Three asymptomatic adolescents presented with low lipid levels detected on screening laboratory studies. Patient 1, a 13 6/12-year-old male and patient 2, a 15 9/12-year-old female, were siblings. Patient 3 was a 12 6/12-year-old female. All had total cholesterol ranging from 61 to 87 mg/dL, low-density lipoprotein cholesterol 10 to 28 mg/dL, and triglycerides 19 to 36 mg/dL. Aspartate transaminase and alanine transaminase levels were normal in patients 1 and 3 and were elevated in patient 2. Liver ultrasounds of patients 2 and 3 showed hepatic steatosis. Molecular testing identified pathogenic variant of apolipoprotein B gene in patients 1 and 2, c.133C>T(p.Arg.45Ter) confirming the diagnosis of h-FHBL. Discussion: More studies are needed in children with h-FHBL and other forms of hypobetalipoproteinemia to improve awareness of these disorders and to develop guidelines for monitoring and risk reduction in affected patients. Conclusion: Health care providers should be aware that persistent hypolipidemia may indicate h-FHBL, which can be a risk factor for liver dysfunction. Youth with h-FHBL should be counseled about lifestyle modifications and screened for the development of metabolic dysfunction-associated steatotic liver disease.

Predictive value of serum alanine aminotransferase for fatty liver associated with metabolic dysfunction.

In this editorial, we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology (2024; 30: 1346-1357). The study highlights a noteworthy association between persistently elevated, yet high-normal levels of alanine transaminase (ALT) and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD has emerged as a globally prevalent chronic liver condition, whose incidence is steadily rising in parallel with improvements in living standards. Left unchecked, MAFLD can progress from hepatic steatosis to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, underscoring the importance of early screening and diagnosis. ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage. While ALT levels demonstrate a significant correlation with the severity of fatty liver disease, they lack specificity. The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels. Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD, emphasizing the need for closer monitoring and potential intervention in such cases.

Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common liver disorder worldwide, with an estimated global prevalence of more than 31%. Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide a comprehensive analysis of the extrahepatic manifestations of MASH, focusing on chronic diseases related to the cardiovascular, muscular, and renal systems. A systematic review of published studies and literature was conducted to summarize the findings related to the systemic impacts of MASLD and MASH. The review focused on the association of MASLD and MASH with metabolic comorbidities, cardiovascular mortality, sarcopenia, and chronic kidney disease. Mechanistic insights into the concept of lipotoxic inflammatory "spill over" from the MASH-affected liver were also explored. MASLD and MASH are highly associated (50%-80%) with other metabolic comorbidities such as impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, and hypertension. Furthermore, more than 90% of obese patients with type 2 diabetes have MASH. Data suggest that in middle-aged individuals (especially those aged 45-54), MASLD is an independent risk factor for cardiovascular mortality, sarcopenia, and chronic kidney disease. The concept of lipotoxic inflammatory "spill over" from the MASH-affected liver plays a crucial role in mediating the systemic pathological effects observed. Understanding the multifaceted impact of MASH on the heart, muscle, and kidney is crucial for early detection and risk stratification. This knowledge is also timely for implementing comprehensive disease management strategies addressing multi-organ involvement in MASH pathogenesis.

Novel insights into autophagy in gastrointestinal pathologies, mechanisms in metabolic dysfunction-associated fatty liver disease and acute liver failure.

In this editorial, we comment on three articles published in a recent issue of World Journal of Gastroenterology. There is a pressing need for new research on autophagy's role in gastrointestinal (GI) disorders, and also novel insights into some liver conditions, such as metabolic dysfunction-associated fatty liver disease (MAFLD) and acute liver failure (ALF). Despite advancements, understanding autophagy's intricate mechanisms and implications in these diseases remains incomplete. Moreover, MAFLD's pathogenesis, encompassing hepatic steatosis and metabolic dysregulation, require further elucidation. Similarly, the mechanisms underlying ALF, a severe hepatic dysfunction, are poorly understood. Innovative studies exploring the interplay between autophagy and GI disorders, as well as defined mechanisms of MAFLD and ALF, are crucial for identifying therapeutic targets and enhancing diagnostic and treatment strategies to mitigate the global burden of these diseases.

Effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease: Clinical implications.

In this editorial, we comment on the article by Chen et al recently published in 2024. We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase (ALT) would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease (MAFLD). This is important given the increasing prevalence of MAFLD and obesity globally. Currently, a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT. The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered, particularly as their study found that 83.12% of their study population with a diagnosis of MAFLD had a normal ALT. The main advantages of screening would be to identify patients and provide intervention early, the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis. However, there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered. Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity, although studies have not yet shown a significant improvement in fibrosis regression. It would also require a huge amount of resource if a reduced ALT level alone was used as criteria; it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk. Currently, there is not a good argument to recommend widespread screening with a reduced ALT level as this is unlikely to be cost-effective. This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories. Although studies previously have suggested a more pragmatic approach in screening those over the age of 60, this is likely to change with the increasing incidence of obesity within the younger age groups. The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.

Diagnostic indicators and lifestyle interventions of metabolic-associated fatty liver disease.

MAFLD has become a major global health problem and is the leading cause of liver disease worldwide. The disease progresses from a simple fatty liver to gradual fibrosis, which progresses to cirrhosis and even hepatocellular liver cancer. However, the methods currently used for diagnosis are invasive and do not facilitate clinical assessment of the condition. As a result, research on markers for the diagnosis of MAFLD is increasing. In addition, there are no clinical medications for the treatment of MAFLD, and lifestyle interventions remain effective in the prevention and treatment of MAFLD. In this review, we attempt to make a summary of the emerging diagnostic indicators and effective lifestyle interventions for MAFLD and to provide new insights into the diagnosis and treatment of MAFLD.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, ß-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Sarcopenia and metabolic dysfunction associated steatotic liver disease: Time to address both.

Sarcopenia and metabolic dysfunction associated steatotic liver disease (MASLD) are closely intertwined. Sarcopenia, traditionally a disease of the older adult and chronic disease population, has been closely studied as one of the pathophysiologic conditions at play in the development of MASLD. They share similar risk factors of insulin resistance and physical inactivity. Given similar pathophysiology along the liver-muscle axis, sarcopenia has been studied as a risk factor for MASLD, and vice versa. Current research suggests a bidirectional relationship. Given the chronicity of MASLD as a chronic inflammatory liver disease, it can break down muscle mass and lead to sarcopenia, while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the liver. However, for the longest time, a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes. A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for study. However, no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified yet. Future studies are needed to reach a consensus and reduce diagnostic variation. With similar pathophysiology and shared risk factors between the two diseases, future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis.

Background: Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM). Method: This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS. Results: The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%. Conclusion: SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.